Search Results (388)

Carbapenems are essential for the treatment of severe infections caused by Gram-negative bacteria, particularly in critically ill and immunocompromised patients. However, the global rise of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii has significantly eroded their effectiveness, and the phenomenon is now recognized as a major public health threat. Resistance is driven by the complex and evolving interplay of enzymatic and non-enzymatic mechanisms, occurring within highly successful clonal lineages and mobile genetic platforms. This review summarizes advances since 2020 in the molecular basis of carbapenem resistance, integrating enzymatic mechanisms across Ambler classes A, B, C, and D with emerging non-enzymatic contributors, including porin remodeling, efflux pump upregulation, target-site alterations, and outer-membrane adaptations. Particular attention is given to adaptive genome dynamics, such as IS26-mediated gene amplification, plasmid multimerization, and heteroresistance, that generate unstable resistance phenotypes and complicate routine susceptibility testing. Newly introduced β-lactam/β-lactamase inhibitor combinations exert distinct selective pressures: ceftazidime–avibactam favors KPC Ω-loop variants and permeability defects, often restoring carbapenem susceptibility, whereas meropenem–vaborbactam and imipenem–relebactam resistance is driven mainly by porin loss and β-lactamase gene amplification. Cefiderocol resistance is multifactorial, frequently involving impaired siderophore uptake and heteroresistance, while sulbactam–durlobactam remains active against OXA-producing A. baumannii but is compromised by metallo-β-lactamases and PBP3 alterations. Carbapenem resistance is increasingly characterized by convergent, multi-layered adaptations that undermine both established and novel therapies. While high-level randomized evidence remains limited for some resistance mechanisms, emerging mechanistic, microbiological, and clinical data support the need for mechanism-aware diagnostics, repeated susceptibility assessment during therapy, and stewardship strategies informed by resistance biology. Integrating molecular context into routine practice will be critical to preserving emerging treatment options and limiting the global impact of carbapenem resistance. Full article

Cefepime combined with late-generation β-lactamase inhibitors—enmetazobactam, zidebactam, and taniborbactam—represents a promising strategy to treat multidrug-resistant Gram-negative infections. These combinations expand the therapeutic armamentarium beyond established β-lactam/β-lactamase inhibitor regimens, offering targeted activity against ESBL-, AmpC-, and carbapenemase-producing Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa. In vitro studies highlight potent and broad activity, with mechanisms including β-lactamase inhibition and, in the case of zidebactam, dual β-lactam enhancement through PBP2 binding. Clinical evidence demonstrates efficacy in complicated urinary tract infections and suggests potential for treating extensively drug-resistant infections, including those unresponsive to conventional β-lactam/β-lactamase inhibitors. Emerging resistance mechanisms—such as PBP alterations, porin loss, efflux pump overexpression, and evolving KPC or NDM variants—underscore the need for ongoing surveillance and robust susceptibility testing. This review provides a comprehensive overview of the mechanisms of action, in vitro activity, pharmacokinetic/pharmacodynamic properties, clinical outcomes, and resistance patterns of these cefepime-based combinations. It also highlights future directions, including the establishment of clinical breakpoints, evaluation in severe infections, and exploration of combination strategies to counteract complex resistance. Overall, these agents exemplify a strategic evolution in β-lactam therapy, offering versatile options to reduce carbapenem reliance while maintaining high efficacy against multidrug-resistant Gram-negative pathogens. Full article

Accelerating decarbonization in hot-climate buildings requires integrated retrofit strategies that address energy performance, environmental impact, thermal comfort, and economic feasibility within a unified decision framework. This study develops and validates a simulation-driven multi-criteria approach to evaluate retrofit packages across three representative ASHRAE hot sub-climates (1B, 2B, 2A). An academic building was modeled using DesignBuilder (Stroud, UK) and validated in accordance with ASHRAE Guidelines. The retrofit analysis integrates envelope enhancements (insulation and reflective coatings), glazing-integrated photovoltaics (GIPV), rooftop photovoltaics (RTPV), and a Dedicated Outdoor Air System (DOAS). The performance evaluation incorporates dynamically simulated energy consumption, operational CO₂ emissions, thermal comfort indicators (PMV and DCH), and techno-economic metrics (IRR, ROI, PBP). Weighting factors were derived from a structured stakeholder consultation to reflect context-sensitive sustainability priorities. The results indicate energy reductions of approximately 51–57% and carbon emission reductions of 40–53% across the examined zones, while discomfort hours decreased by roughly 42–46%. This demonstrates significant improvements in thermal comfort under integrated retrofit strategies, particularly with DOAS integration, highlighting the importance of ventilation-driven comfort enhancement. Economic feasibility was climate-dependent; envelope-focused solutions yielded high returns, while integrated strategies delivered balanced environmental and economic performance. The proposed framework enables systematic, climate-specific prioritization of retrofit alternatives and supports scalable, economically viable NZEB transitions in rapidly expanding hot-climate educational infrastructure. Full article

To address the stringent emission regulations of the International Maritime Organization (IMO) and the growing demand for green port operations, this study proposes an innovative range-extended series hybrid powertrain system featuring a dedicated methanol engine as an Auxiliary Power Unit (APU) for harbor tugs. Based on an analysis of actual ship operational data, a core design paradigm of “battery-dominant, engine-as-range-extender” is established. A robust capacity parameter matching method is proposed, yielding a configuration comprising a 200 kW∙h/600 kW Lithium Iron Phosphate Battery Pack (LFPBP), a 250 kW methanol APU, and a 400/600 kW Permanent Magnet Synchronous Propulsion Motor (PMSM). A hierarchical intelligent energy management strategy (EMS), integrating state-machine coordination and real-time power allocation, is designed. High-fidelity simulations under a typical duty cycle demonstrate that the proposed system achieves an equivalent fuel-saving rate of 50.8% compared with a conventional diesel system, with the engine operating exclusively in its high-efficiency zone (>42% efficiency) for only 35% of the operational time. A full life-cycle techno-economic analysis reveals an incremental investment payback period (PBP) of approximately 3 months and a net present value (NPV) exceeding USD 9.69 million over a 10-year period. Quantitative environmental analysis shows an annual reduction of approximately 94.8% in CO₂ emissions (assuming the use of green methanol produced from renewable sources and captured CO₂), 95% in NO_x emissions, and the near-elimination of SO_x and particulate matter (PM). This study provides a systematic and economically attractive solution with promising engineering feasibility verified by simulation, which paves the way for further experimental validation and practical engineering implementation. Full article

Fiber Bragg Gratings (FBGs) are essential components in fiber-optic sensing systems owing to their high sensitivity, compact structure, and immunity to electromagnetic interference, and have been widely applied in structural health monitoring, aerospace, energy, and biomedical fields. Conventional FBG fabrication methods, including standing-wave, two-beam interference and phase mask methods, rely heavily on the photosensitivity of optical fibers and are limited in terms of fabrication flexibility and grating structural diversity. Femtosecond Laser Direct Writing (FLDW) has emerged as a prospective approach for FBG fabrication due to its nonlinear absorption mechanism, low thermal damage, three-dimensional processing capability and broad material compatibility. This review summarizes recent progress in FLDW-FBGs, with particular emphasis on the characteristics of point-by-point (PbP), line-by-line (LbL) and plane-by-plane (Pl-by-Pl) methods. The implementation of these methods in various fiber, including standard single-mode fibers, sapphire fibers, and polymer optical fibers, is discussed in detail. In addition, recent advances in FBG-based sensing applications under extreme environments, as well as in biomedical sensing and optical fiber communication, are reviewed. Key challenges related to fabrication efficiency, process stability, and microstructural characterization are further analyzed. Finally, potential development directions toward improved controllability, structural design flexibility, and engineering applicability of FLDW-FBGs are outlined. Full article

The variegated cutworm Peridroma saucia Hübner, a recently emerged polyphagous pest in China’s Huang-Huai River Basin, uses sex pheromones (Z)-11-hexadecenyl acetate (Z11-16: Ac) and (Z)-9-tetradecenyl acetate (Z9-14: Ac) for mate finding. Insect pheromone-binding proteins (PBPs) serve as the primary filter for detecting specific sex pheromones. Although comprehensive functional analyses of PBPs exist, their binding mechanisms remain poorly characterized. In this study, we elucidated the binding properties and mechanisms of PsauPBP3 in sex pheromone recognition by computational and experimental approaches. PsauPBP3, predominantly expressed in male P. saucia antennae, showed high binding affinity for both Z11-16: Ac and Z9-14: Ac, as demonstrated by binding-free-energy calculations and fluorescence binding assays. Molecular dynamics simulations and docking studies identified five key residues (Thr-10, Phe-13, Ile-53, Ile-95, and Phe-119) that consistently interact with these pheromones, indicating their critical role in ligand binding. Computational alanine scanning further demonstrated that all five residues act as binding determinants, with Phe-13 and Ile-95 making particularly significant contributions to ligand affinity. The results were further validated by site-directed mutagenesis and fluorescence binding assays. This work provides insights into the function and binding mechanisms of PBPs in sex pheromone recognition and supports the development of targeted mating disruption strategies for P. saucia control. Full article

Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are high-burden healthcare-associated pathogens that increase mortality, prolong hospitalisation, and drive substantial healthcare costs worldwide. These infections are associated with high morbidity, increased mortality, prolonged hospital stays, and significant costs, particularly among immunocompromised patients or those with extended hospitalizations. This systematic review was conducted and reported in accordance with PRISMA 2020, aiming to synthesise existing data on the epidemiology, resistance mechanisms, clinical manifestations, and strategies for the diagnosis, treatment, and prevention of MRSA and VRE infections. Data were qualitatively synthesised. A total of 113 records published between 2020 and 2025 met the inclusion criteria and were identified through searches in multiple bibliographic databases and publisher platforms (e.g., PubMed, Scopus, Web of Science). MRSA and VRE are implicated in numerous severe infections, including ventilator-associated pneumonia, catheter-associated urinary tract infections, endocarditis, and bacteraemia. Antimicrobial resistance is driven by the mecA, vanA, and vanB genes, while biofilm formation further complicates therapeutic efforts. Biofilm formation can promote antibiotic tolerance (slower killing without an increase in MIC) and persistence (survival of ‘persister’ cells), distinct from genetic resistance, and may complicate therapy in selected infections. Effective strategies include appropriate anti-MRSA/anti-VRE agents (e.g., ceftaroline for MRSA; linezolid or daptomycin for VRE), active screening, stringent infection prevention and control measures, and antimicrobial stewardship programmes. Implementation is often hindered by institutional barriers, limited resources, and insufficient staff training. A multidisciplinary, evidence-based approach is essential for the effective management of these infections. Reducing this burden requires coordinated implementation of rapid diagnostics, stringent infection prevention and control, and antimicrobial stewardship, supported by sustained institutional and public health investment. Full article

The venom of the Asian hornet (Vespa affinis) comprises a complex mixture of biologically active substances, including various enzymes such as phospholipase A and hyaluronidase; amines such as histamine, serotonin, and catecholamines; peptides such as mastoparan and vespakinin; and other components including acetylcholine and antigen 5. This complexity reflects the highly evolved nature of V. affinis as a venomous insect. The composition of animal venoms often exhibits a certain degree of variability, making the study of biogenic amines particularly intriguing. The objective of this research was to confirm and identify the presence of tetradecylamine in the venom of Vespa affinis using the scientific computational analysis software MetFrag. In addition, the study aimed to construct the biosynthetic pathway of this compound and to predict its potential biological roles. The predicted biosynthetic route of tetradecylamine suggested its possible involvement in antibacterial activity. Antibacterial assays were performed against four bacterial strains Escherichia coli, Staphylococcus aureus, Bacillus cereus, and Klebsiella pneumoniae. The results revealed that tetradecylamine exhibited notable inhibitory effects, with minimum inhibitory concentration (MIC) values of 2, 4, 8, and 4 µg/mL, and minimum bactericidal concentration (MBC) values of 2, 4, 8, and 4 µg/mL, respectively. Furthermore, molecular docking studies were conducted using penicillin-binding protein 2x (PBP2x, PDB ID: 5OIZ) as the target protein. Among eight tested ligands, streptomycin exhibited the highest binding affinity with a docking score of 64.76. In contrast, biogenic amines such as 2-phenylethylamine and tetradecylamine showed docking scores of 33.74 and 48.2, respectively. In the MurA protein (PDB ID: 3VCY), the biogenic amine ligand tetradecylamine exhibited a binding affinity comparable to that of certain reference drugs. Specifically, tetradecylamine achieved a GOLD score of 52.58, whereas ampicillin showed a higher score of 61.53. Notably, tetradecylamine demonstrated a higher binding affinity to the target protein compared with certain conventional antibiotics such as doxycycline and gentamycin. Full article

Anion exchange membrane water electrolysis (AEMWE) is promising for low-cost hydrogen production, but its progress is limited by the weak mechanical strength and structural instability of polymer membranes. Here, a PPS-PBP/PVA composite membrane was developed using a polyphenylene sulfide (PPS) mesh as the mechanical scaffold, poly(biphenyl piperidinium) (PBP) as the ion-conducting polymer, and poly(vinyl alcohol) (PVA) as an interfacial binder. The membrane shows significantly enhanced tensile strength and puncture resistance, reduced swelling, and improved interfacial integrity. The optimized PPS-PBP/PVA (10 wt%) membrane delivers 6 A cm⁻² at 2.16 V in 1 M KOH at 80 °C and maintains stable operation for 500 h at 1 A cm⁻² with only a slight voltage increase. The results demonstrate that reinforcement coupled with interface regulation is an effective approach to constructing robust and durable composite membranes for AEMWE. Full article

Background/Objectives: Granulicatella adiacens infective endocarditis is conventionally managed with penicillin, ampicillin, or ceftriaxone in combination with gentamicin, although double beta-lactam regiments have been proposed a safer alternative to reduce aminoglycoside-associated nephrotoxicity. To date, the High-Molecular-Mass Penicillin-Binding Proteins (HMM-PBPs) of G. adiacens and their affinities for beta-lactam antibiotics have not been previously characterized. This study investigated the HMM-PBP profile of G. adiacens, with particular interest on sequence alterations and beta-lactam binding properties, both as single agents and in combination. Methods: Beta-lactam activity, synergistic interactions and PBP binding affinities were evaluated in a clinical isolate (IS 48) and compared with those in the reference strain ATCC 49175. Binding of PBPs to ampicillin, ceftriaxone, and ceftobiprole, alone or in combination, was investigated by Bocillin-FL labeling. PBP homology and conserved active-sites motifs were assessed by sequence alignment, and pbp gene mutations were identified by whole-genome sequencing. Results: The clinical isolate was non-susceptible to ampicillin, resistant to ceftriaxone and exhibited higher minimum inhibitory concentrations (MICs) for ceftobiprole relative to the fully susceptible ATCC reference strain. Five HMM PBPs with high enterococcal homology, were identified. In the IS 48 isolate, the class A PBP showed distinct amino acid substitutions in proximity to the catalytic centers. Despite these alterations, PBP1A and PBP2A were strongly inhibited by the tested beta-lactams, whereas PBP2 and PBP2B demonstrated low acylation rates. Combination of ampicillin with either ceftobiprole or ceftriaxone resulted in enhanced acylation of the three bifunctional HMM PBPs compared with monotreatment. IC₅₀ values were consistently higher for the IS 48 clinical isolate, suggesting decreased target availability and/or reduced beta-lactam affinity under clinical conditions. Conclusions: The resistance phenotype of G. adiacens clinical isolate appears to be primarily associated with altered PBP beta-lactam interactions. Nonetheless, beta-lactam combination regimes remain effective by achieving substantial inhibition of key HMM-PBPs involved in peptidoglycan synthesis, thereby supporting the rationale for dual beta-lactam therapy in this setting. Full article

Background: Food allergy (FA) is an emerging problem in pediatrics, with tree nuts and peanuts being frequent causes of severe reactions. Oral food challenge (OFC) remains the gold standard for diagnosing FA. However, it is a stressful treatment and not always risk-free. Objectives: To identify potential biomarkers, using component-resolved diagnosis (CRD) associated with OFC outcome in children with tree nut (hazelnut, walnut, almond, and pistachio) and peanut allergy, who live in central and southern Italy. Methods: Eighty-eight (1–18 years) children followed at the Pediatric Allergy Clinic of Policlinico Umberto I in Rome were included in this study. All patients underwent skin prick tests (SPTs), prick-by-prick (PbP) tests, and serum-specific Immunoglobulin E (sIgE) measurement to allergenic components using CRDs. Results: In hazelnut allergy (n = 60 OFCs), OFC failure occurred in 41 children. Higher sIgE levels to Cor a 8 (OR 2.04, 95% CI 1.17–3.55), Cor a 9 (OR 2.61, 95% CI 1.37–5.00), and Cor a 14 (OR 1.65, 95% CI 1.14–2.38) were all significantly associated with an increased probability of a positive OFC outcome. In peanut allergy (n = 30 OFCs), OFC failure occurred in 16 children. Ara h 9 was the only statistically significant predictor of OFC failure, showing a very wide confidence interval (OR, 95% CI: 1.116–484). For walnut, almond, and pistachio, sample sizes were insufficient to support inferential modeling. Conclusions: CRD biomarkers can stratify the likelihood of OFC reactions in pediatric FA, enhancing clinical decision-making and reducing unnecessary challenges. Full article

Municipal solid waste challenges (MSW) and concerns about fossil fuel dependence motivate efforts to recover energy from waste, including refuse-derived fuel (RDF). Techno-economic assessment (TEA) evaluates the feasibility of systems by quantifying investment performance. However, most RDF-TEA studies typically rely on isolated sensitivity analyses. That provides limited insight into interaction effects in emerging markets. This study maps the multivariable feasibility of RDF production from MSW in Ghana under realistic economic conditions. Using a pilot-calibrated case study, the assessment integrates discounted cash flow analysis with response surface methodology–design of experiment (RSM-DoE). A central composite design evaluates interaction effects among operational and economic variables for a system capacity of 2875 tonnes RDF/year. The results indicate economic viability with a net present value (NPV) of USD 892,556.44, a payback period (PBP) of 6.61 years and a levelised production cost (LPC) of USD 18.96/tonne. The RSM models show high explanatory power (R², R²adj, R²pred > 90%). Sensitivity results demonstrate that support mechanisms can significantly reduce LPC and PBP while preserving investment viability. The study quantifies the feasibility thresholds and the support instruments within the RDF design levers. It further provides a transferable framework for assessing deployment and upscaling in emerging markets. The findings highlight the need for structured pricing mechanisms and regulatory support for the long-term sustainability of RDF as an AF. Full article

This review focuses on the research progress on natural products as β-lactam antibiotic adjuvants, aiming to address the escalating challenge of antibiotic resistance, particularly the inactivation of antibiotics caused by β-lactamases. The article provides an in-depth analysis of the mechanisms by which plant-derived (e.g., flavonoids, tannins, phenolics, terpenoids, and alkaloids) and microbial-derived (e.g., clavulanic acid, fungal metabolites, bacteriophages) natural products enhance antimicrobial efficacy. Key potentiation strategies discussed include efflux pump inhibition, membrane permeability alteration, biofilm disruption, PBP2a inhibition, and direct β-lactamase inhibition. Additionally, the review outlines in vitro methods (e.g., dilution and checkerboard assays) and in vivo models (e.g., mouse infection models) used to assess synergistic effects. It also addresses major challenges in identifying active compounds, elucidating mechanisms of action, and pharmacokinetic characterization. Looking forward, the article highlights the potential of multi-omics approaches, artificial intelligence, and nanotechnology to overcome existing bottlenecks, providing novel strategies for the development of effective and safe antibiotic adjuvants. These advances are expected to provide both theoretical insights and practical guidance for combating antibiotic-resistant bacterial infections. Full article

The emergence of multidrug-resistant (MDR) bacterial pathogens has heightened the urgency for novel antibacterial agents. The bacterial cell wall usually comprises peptidoglycan, which presents a prime target for antibacterial drug development due to its indispensable role in maintaining cellular integrity. Conventional antibiotics such as β-lactams and glycopeptides hinder peptidoglycan synthesis through competitive binding of penicillin-binding proteins (PBPs) and sequestration of lipid-linked precursor molecules. Nevertheless, prevalent resistance mechanisms including target modification, β-lactamase hydrolysis, and multi-drug efflux pumps have limited their clinical utility. This comprehensive analysis explicates the molecular machinery underlying bacterial cell wall assembly, evaluates both explored and unexplored enzymatic nodes within this pathway, and highlights the transformative impact of high-resolution structural elucidation in accelerating structure-guided drug discovery. Novel targets such as GlmS, GlmM, GlmU, Mur ligases, D,L-transpeptidases are assessed for their inclusiveness for the discovery of next-generation antibiotics. Additionally, cell wall inhibitors are also examined for their mechanisms of action and evolutionary constraints on MDR development. High-resolution crystallographic data provide valuable insights into molecular blueprints for structure-guided optimization of pharmacophores, enhancing binding affinity and circumventing resistance determinants. This review proposes a roadmap for future innovation, advocating for the convergence of computational biology platforms, machine learning-driven compound screening, and nanoscale delivery systems to improve therapeutic efficacy and pharmacokinetics. The synergy of structural insights and cutting-edge technologies offers a multidisciplinary framework for revitalizing the antibacterial arsenal and combating MDR infections efficiently. Full article

Fisheries bycatch, while representing a major ecological concern due to the incidental capture of non-target species, also constitutes an underexplored source of marine biomass with biotechnological potential. This study aimed to generate and characterize bioactive peptides from the muscle tissue of three common bycatch species from the Brazilian coast: Paralonchurus brasiliensis, Micropogonias furnieri, and Hepatus pudibundus. Muscle homogenates were hydrolyzed using either Alcalase or Protamex to produce peptide-rich hydrolysates, which were analyzed through SDS-PAGE, HPLC-UV, MALDI-TOF, and LC-MS/MS. De novo sequencing and bioinformatic analyses predicted bioactivities that were subsequently validated by in vitro assays. The results demonstrated that enzyme selection strongly influenced both peptide profiles and bioactivity. The Protamex hydrolysate of P. brasiliensis (PBP) exhibited potent antifungal activity, inhibiting Candida albicans growth by 81%, whereas the Alcalase hydrolysate (PBA) showed moderate inhibition of Staphylococcus aureus (29%). No significant effect was observed against Escherichia coli. Overall, this study highlights a sustainable strategy for the valorization of fisheries bycatch through the production of bioactive marine peptides and identifies P. brasiliensis hydrolyzed with Protamex as a promising source of anti-Candida peptides for pharmaceutical and nutraceutical applications. Full article